TY - JOUR
T1 - Metabolite profiling of CKD progression in the chronic renal insufficiency cohort study
AU - Wen, Donghai
AU - Zheng, Zihe
AU - Surapaneni, Aditya
AU - Yu, Bing
AU - Zhou, Linda
AU - Zhou, Wen
AU - Xie, Dawei
AU - Shou, Haochang
AU - Avila-Pacheco, Julian
AU - Kalim, Sahir
AU - He, Jiang
AU - Hsu, Chi Yuan
AU - Parsa, Afshin
AU - Rao, Panduranga
AU - Sondheimer, James
AU - Townsend, Raymond
AU - Waikar, Sushrut S.
AU - Rebholz, Casey M.
AU - Denburg, Michelle R.
AU - Kimmel, Paul L.
AU - Vasan, Ramachandran S.
AU - Clish, Clary B.
AU - Coresh, Josef
AU - Feldman, Harold I.
AU - Grams, Morgan E.
AU - Rhee, Eugene P.
N1 - Publisher Copyright:
© 2022, Wen et al. This is.
PY - 2022/10/24
Y1 - 2022/10/24
N2 - BACKGROUND. Metabolomic profiling in individuals with chronic kidney disease (CKD) has the potential to identify novel biomarkers and provide insight into disease pathogenesis. METHODS. We examined the association between blood metabolites and CKD progression, defined as the subsequent development of end-stage renal disease (ESRD) or estimated glomerular filtrate rate (eGFR) halving, in 1,773 participants of the Chronic Renal Insufficiency Cohort (CRIC) study, 962 participants of the African-American Study of Kidney Disease and Hypertension (AASK), and 5,305 participants of the Atherosclerosis Risk in Communities (ARIC) study. RESULTS. In CRIC, more than half of the measured metabolites were associated with CKD progression in minimally adjusted Cox proportional hazards models, but the number and strength of associations were markedly attenuated by serial adjustment for covariates, particularly eGFR. Ten metabolites were significantly associated with CKD progression in fully adjusted models in CRIC; 3 of these metabolites were also significant in fully adjusted models in AASK and ARIC, highlighting potential markers of glomerular filtration (pseudouridine), histamine metabolism (methylimidazoleacetate), and azotemia (homocitrulline). Our findings also highlight N-acetylserine as a potential marker of kidney tubular function, with significant associations with CKD progression observed in CRIC and ARIC. CONCLUSION. Our findings demonstrate the application of metabolomics to identify potential biomarkers and causal pathways in CKD progression.
AB - BACKGROUND. Metabolomic profiling in individuals with chronic kidney disease (CKD) has the potential to identify novel biomarkers and provide insight into disease pathogenesis. METHODS. We examined the association between blood metabolites and CKD progression, defined as the subsequent development of end-stage renal disease (ESRD) or estimated glomerular filtrate rate (eGFR) halving, in 1,773 participants of the Chronic Renal Insufficiency Cohort (CRIC) study, 962 participants of the African-American Study of Kidney Disease and Hypertension (AASK), and 5,305 participants of the Atherosclerosis Risk in Communities (ARIC) study. RESULTS. In CRIC, more than half of the measured metabolites were associated with CKD progression in minimally adjusted Cox proportional hazards models, but the number and strength of associations were markedly attenuated by serial adjustment for covariates, particularly eGFR. Ten metabolites were significantly associated with CKD progression in fully adjusted models in CRIC; 3 of these metabolites were also significant in fully adjusted models in AASK and ARIC, highlighting potential markers of glomerular filtration (pseudouridine), histamine metabolism (methylimidazoleacetate), and azotemia (homocitrulline). Our findings also highlight N-acetylserine as a potential marker of kidney tubular function, with significant associations with CKD progression observed in CRIC and ARIC. CONCLUSION. Our findings demonstrate the application of metabolomics to identify potential biomarkers and causal pathways in CKD progression.
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U2 - 10.1172/jci.insight.161696
DO - 10.1172/jci.insight.161696
M3 - Article
C2 - 36048534
AN - SCOPUS:85140417157
SN - 2379-3708
VL - 7
JO - JCI Insight
JF - JCI Insight
IS - 20
M1 - e161696
ER -